Malaria has a tremendous impact on human health, killing millions annually and the disease is a major impediment for social and economic development of nations in malaria-endemic areas, particularly in sub-Saharan Africa (1, see the appended Citations). Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes (2), transform into liver stages, and subsequent liver stage development ultimately results in release of pathogenic merozoites (3).
Because an effective ‘subunit’ malaria vaccine has remained elusive and the complexity of the malaria parasite Plasmodium might preclude the successful development of such a vaccine, whole organism vaccine approaches against malaria have lately found renewed interest (4). The feasibility of such a vaccine has been demonstrated in animal models and subsequently in humans by induction of sterile protective immunity through inoculation with irradiation-attenuated parasites (5, 6). Liver stages are a prime malaria vaccine target because they can be completely eliminated by sterilizing immune responses, thereby preventing malaria infection (7). The recent availability of complete Plasmodium genome sequences (8, 9) may now permit the development of live-attenuated parasites by more precise and defined genetic manipulations (10).
Using expression profiling, we identified genes that are specifically expressed during the pre-erythrocytic part of the parasite life cycle (11, 12). A number of pre-erythrocytic genes named UIS (up-regulated in infective sporozoites) also showed up-regulation in sporozoites when they gain infectivity for the mammalian host (11).